The proposed research will investigate the feasibility of utilizing inherent properties of the infection site as a means to activate antifungal prodrugs selectively. Prodrug derivatives of an antifungal agent will be prepared and tested for their susceptibility to activation by conditions present at infection sites of C. albicans. Test compounds will be analyzed both in vitro and in vivo to determine their selectivity for the fungal infection. Promising leads will be those compounds which are both easily activated by these conditions and are resistant to activation in the normal mammalian physiological environment. Phase II will optimize the prodrug design based on our lead candidates and take this second generation design into preclinical testing.